Effects of exercise-based interventions on gluteal tendinopathy. Systematic review with meta-analysis

The objective of this review was to evaluate the effect of exercise on pain intensity, function, and quality of life in individuals with gluteal tendinopathy. Searches were carried out in PUBMED, EMBASE, CINAHL, Cochrane Library, and PEDro databases. Randomized or quasi-randomized controlled trials were included. Five studies met the eligibility criteria, comparing exercise-based interventions with minimal interventions and/or corticosteroid injections. Three studies, involving 383 participants, were included in the quantitative analysis. Meta-analyses showed that exercise is superior to minimal intervention for function in short-term [mean difference (MD) = 10.24; 95% confidence interval (95%CI) = 5.98, 14.50) and long-term (MD = 6.54; 95%CI = 1.88, 11.21]). However, no difference was observed for quality of life in the short [standardized mean difference (SMD) = 0.33; 95%CI = −0.29, 0.94] and long-term (SMD = 0.11; 95%CI = −0.16, 0.37). The effect of exercise was no different from that of corticosteroid injections for pain intensity in the short (MD = 1.25; 95%CI = −3.56, 6.05) and long-term (MD = −1.37; 95%CI = −3.72, 0.98]). In conclusion, exercise is superior to minimal interventions for function in the short- and long-term in individuals with gluteal tendinopathy. Exercise and corticosteroid injections had similar effects on pain intensity, however, exercise showed a higher treatment success rate when compared to corticosteroid injections in this population. The GRADE analysis revealed that the certainty of the evidence ranges from low to very low, therefore, large high-quality randomized controlled trials are recommended. PROSPERO registration number: CRD42021242853.


Selection criteria for included studies
Study design Systematic review with meta-analysis which included randomized and quasi-randomized controlled trials.Studies with other types of study designs, such as case series and case reports, were excluded.

Population
Studies that evaluated patients diagnosed with gluteal tendinopathy, greater trochanteric pain syndrome, trochanteric bursitis or nonspecific lateral hip pain 7,25 , diagnosed clinically, with or without abnormal imaging findings were included.For inclusion, participants had to be over 18 years old, of both sexes, with any level of physical activity.Studies involving patients diagnosed with hip osteoarthritis, femoroacetabular impingement, partial or complete rupture of the gluteal tendons, labrum injuries, avascular necrosis of the femoral head, hip fractures, peripheral nerve dysfunctions (such as lateral femoral cutaneous nerve entrapment), rheumatological diseases and/or tumors were excluded.

Interventions and comparisons
Studies that carried out interventions based on progressive load resistance exercises, with concentric, eccentric, and/or isometric contractions in at least one of the groups were included.Resistance training could have been carried out in isolation or combined with other treatments, supervised by health professionals or unsupervised, using any progression methods.Studies were considered eligible if they compared an exercise group to: other exercise-based interventions, placebo/sham interventions, no intervention (such as 'wait and see' approach), education, electrothermophototherapeutic interventions (modalities such as extracorporeal shockwave therapy, ultrasound, etc.), invasive interventions (such as corticosteroid or platelet rich plasma injections), or any other type of conservative or surgical intervention.

Outcomes
The primary outcomes were: pain intensity [Visual Analogue Scale (VAS) and Numerical Pain Rating Scale (NPRS)]; function [Victorian Institute of Sport Assessment-Gluteal tendons (VISA-G), Oxford Hip Score (OHS) and Lateral Hip Pain Questionnaire (LHPQ)]; perception of change [Global Rating of Change Scale (GROC)] and quality of life [Assessment of Quality of Life (AQoL) and Quality of Life Questionnaire (EQ-5D)].
Secondary outcomes were: participation in activities [Active Australia Survey (AAS) and International Physical Activity Questionnaire-Short Form (IPAQ-SF)]; strength (dynamometry); biomechanical variables (kinematics and kinetics of the pelvis, trunk and lower limbs); and pain catastrophizing [Pain Catastrophizing Scale (PCS)].Studies that included assessments of any of these outcomes using the aforementioned instruments, or any validated and reliable instrument, were included.

Electronic search
The databases Cochrane Central Register of Controlled Trials (CENTRAL, Cochrane Library), Medical Literature Analysis and Retrieval System Online (MEDLINE, via PubMed), Cumulative Index to Nursing and Allied Health Literature (CINAHL, via EBSCO HOST), Excerpta Medica dataBASE (Embase), and Physiotherapy Evidence Database (PEDro) were searched on March 30, 2021 and the searches were updated on March 3, 2022.No language or date restrictions were applied.Search strategies were developed using relevant keywords, which were combined with Boolean terms (see Suppl.Appendix A for complete search strategy).

Study selection
All publications identified in the databases were exported to the Rayyan software (Rayyan QCRI/web app) to remove duplicates and for the study eligibility assessment process.Two reviewers (TTPC and EABR) independently evaluated all articles, initially by titles and abstracts.After this stage, the full texts of potentially relevant studies were evaluated by the same two reviewers.In addition to the electronic search, a manual search of reference lists of the included studies and of review articles was performed to identify other potentially relevant studies.All included articles were discussed to minimize the risk of bias, as recommended by the Cochrane Manual for Systematic Reviews of Interventions 26 .Disagreements regarding the eligibility of studies were discussed and resolved by consensus and, if disagreement persisted, a third reviewer was contacted (RSS).In cases where eligibility criteria were unclear, authors were contacted by email.

Data extraction
Data extraction was performed independently by two reviewers (TTPC and EABR) 26 .When consensus could not be reached, the decision was determined by a third reviewer (RSS).Data were extracted using a standardized form, prepared following the instructions of the data collection form for intervention reviews, developed by Cochrane 27 .
The following items were extracted: objective and study design, sample size, inclusion and exclusion criteria, follow-up time, randomization method, allocation concealment, blinding and other strategies to minimize the risk of bias; patient demographic data; intervention details, such as treatment and session duration, session frequency, dosage of interventions and co-interventions; outcomes of interest, such as pain, function, perception of change, quality of life, strength, participation in activities, pain catastrophizing, and adverse events, including the times at which they were measured; number of participants in each group, calculation of sample size and power.Data regarding differences between the post-intervention groups in the short, medium, and long term were extracted.Categorical and continuous outcomes, confidence intervals, imputation of missing data, and missing data at each time point were considered.In cases of missing data, the authors were contacted by email, with a request to share the results.

Risk of bias
The Physiotherapy Evidence Based Database (PEDro) scale was used to evaluate the methodological quality of the studies 28,29 .The evaluation of the included studies was also carried out independently by two reviewers (TTPC and EABR) 26 , and when consensus could not be reached, the decision was determined by a third evaluator (RSS).At the end of the evaluations, the scores were compared with the results from the PEDro database and there was no divergence between the evaluated scores and the scores obtained from the PEDro database.In terms of study methodological quality, it has been suggested that studies with a score < 4 are considered poor, between 4 and 5 are considered fair, 6 to 8 are considered good, and between 9 and 10 are considered excellent 30,31 .

Data analysis
Whenever possible, data were grouped, and meta-analysis was performed using the random effects model and presented in a forest-plot graph.Results were displayed as mean difference (MD) and 95% confidence intervals (95%CI) when studies used the same scales.Otherwise, effects were calculated using standardized mean difference (SMD) and 95% CI.Chi 2 and I 2 statistics were used to measure heterogeneity between the analyzes.All analyzes were performed using Review Manager software, version 5.4.For effect measures, short-term effects were considered when follow-up was ≤ 12 weeks and long-term effects were considered for follow-up ≥ 26 weeks.
Finally, the assessment of the strength of the evidence was carried out using the Grading of Recommendations Assessment (GRADE) approach 32 through the GRADE PRO software 33 .As this was a systematic review of randomized clinical trials, downgrade criteria were used.Downgrade for each of the following items was considered: risk of bias, when > 25% of participants were from studies with high risk of bias (PEDro score < 6/10) 34 ; imprecision, when the total sample was < 400 35 ; serious inconsistency of results, when the I 2 statistic was greater than 50% or when grouping was not possible 26 ; and indirect evidence, when there were comparisons between different populations and interventions 36 .Publication bias could not be assessed as fewer than ten studies were included 35 .After evaluating all domains, the certainty of the evidence was classified into one of the following levels 36 : high certainty (very confident that the true effect is close to the estimated effect); moderate certainty (moderately confident that the true effect is likely to be close to the effect estimate, but there is a possibility that it will be substantially different); low certainty (confidence in the effect estimate is limited and the true effect may be substantially different from the effect estimate); very low certainty (little confidence in the effect estimate and the true effect is likely to be substantially different from the effect estimate) 32 .

Results
The electronic search identified 1,923 studies.Twenty-three studies had the full text read and 18 were excluded for not meeting the eligibility criteria.Detailed reasons for exclusion are described in Fig. 1.Finally, five studies were included for analysis.Qualitative results regarding samples, interventions, outcomes, and adverse events are described in Table 1.Data regarding the methodological characteristics of the included studies are presented in Table 2.

Patient characteristics
The total number of patients involved in this review was 747, with sample sizes ranging from 30 to 229 patients in the different studies (average sample size = 118.3).The mean age of the patients was 56.9 ± 5.8 years (range 47.6-61.8)and 582 (78%) were women.The average dropout rate from studies was 10.8 ± 8.1% (range 6.9-23.3).

Outcome measures
Pain intensity was assessed with the NRS [37][38][39] .Function and disability were the outcomes that presented the greatest variability in measurement instruments, being assessed by the Hip Disability and Osteoarthritis Outcome Score (HOOS) 37,40,41 , VISA-G 37,38,40,41 , OHS 40,41 , LHPQ 38,41 , Patient Specific Functional Scale (PSFS) 38 .The perception of change was assessed using the GROC 38,39,41,42 and the Likert Scale 39 .The EQ-5D 37,38 and AQol 40,41 were used to assess quality of life.The level of physical activity was assessed by the IPAQ 37 and AAS 38 .Pain catastrophizing was assessed with the PCS 37,38 and for strength assessments isometric torque was measured 38 .No outcome measures were found for biomechanical analyses.

Methodological quality and certainty of evidence
The average score of the studies in the methodological quality and risk of bias assessment was 6.8 ± 1.7 points, ranging from 5 to 9 points (Table 3).Two studies presented a higher risk of bias 37,39 .The least scored topics were subject blinding (not scored by 3 studies) [37][38][39] , therapist blinding (not scored by 5 studies) [37][38][39][40][41] and rater blindness (not scored by 2 studies) 37,39 .The analysis of the certainty of evidence in relation to the results of this review showed a range from low certainty of evidence to very low certainty of evidence (Table 4).

Effects of exercise compared to corticosteroid injections for pain intensity
In the pain intensity analyses, the meta-analysis showed that the effect of exercise was not different from corticosteroid injections in the short-term (MD = 1.25 [95%CI = −3.56,6.05]; p = 0.61; n = 286) and long-term  2C).High heterogeneity was identified in these shortterm (I 2 = 99%) and long-term (I 2 = 93%) analyses (Fig. 2C).GRADE analysis revealed low certainty of evidence (Table 4).

Secondary outcomes, subgroup and sensitivity analyses
A quantitative analysis of secondary outcomes was planned; however, meta-analyses were not possible since no more than one study was found assessing these outcomes.One good quality study 38 found that exercise had a higher treatment success rate when compared to corticosteroid injection (MD = 19.9%[95%CI = 4.7, 35.0]) and to wait-and-see (MD = 49.1% [95%CI = 34.6,63.5]) in the short-term (8 weeks).In the long-term analysis (52 weeks), the exercise group also showed a higher treatment success rate when compared to corticosteroid injection (MD = 20.4% [95%CI = 4.9, 35.9]) and to wait-and-see (MD = 26.8%[95%CI = 11.3,42.3]).Corticosteroid injection had a higher treatment success rate when compared to wait-and-see (MD = 29.2%[95%CI = 13.2, 45.2]) in the short-term (8 weeks) but in the long-term (52 weeks) there was no difference in treatment success rate between corticosteroid injection and wait-and-see (MD = 6.4% [95%CI = − 10.7, 23.6]) 38 .Hip abductor strength was significantly higher after 8 weeks of an exercise intervention in relation to waitand-see (MD = 0.1 Nm/kg [95%CI = 0.01, 0.2]) in a study with good methodological quality 38 .However, no difference was observed between corticosteroid injection and wait-and-see (MD = 0.1 Nm/kg [95%CI = −0.02,0.2]) or between exercise and corticosteroid injection (MD = 0.02 Nm/kg [95%CI = −0.1,0.1]) 38 .With regards to pain catastrophizing, one good quality study found that exercise was superior to wait-and-see in the short-term (MD = −2.6 [95%CI = −5.0,−0.1]), however, no difference was observed between exercise and corticosteroid injections (MD = −1.7 [95%CI = −4.1,0.7]) or between corticosteroid injections and wait-and-see (MD = −0.8[95%CI = −3.0,1.3]) for this outcome 38 .Adverse events associated with the interventions of the studies included in this review were uncommon and more frequently involved a short-term increase in pain (Table 1).None of the sensitivity and subgroup analyses to explore the potential impact of high risk of bias, therapy dosage, exercise type, and population characteristics were investigated due to the small number of included studies.

Discussion
The present review investigated the effects of exercise-based interventions on pain intensity, function, and quality of life in patients with gluteal tendinopathy.The main result of this study is that exercise is superior to minimal intervention (sham exercise or wait-and-see) for function/symptom severity in patients with gluteal tendinopathy in the short-and long-term.However, no difference was observed between these interventions for short-and long-term quality of life.Similarly, the effect of exercise was no different from corticosteroid injections for pain intensity in the short-and long-term, however, exercise showed a higher treatment success rate when compared to corticosteroid infiltration both in the short-and long-term in individuals with gluteal tendinopathy.Overall, there was high heterogeneity in the studies, except for comparisons between exercise and minimal intervention.There was also low or very low certainty of evidence for these comparisons.Management of tendinopathies generally involves exercise as the first line of treatment [15][16][17]19 and exercise has been shown to improve functional outcomes in different tendinopathies 23,42,43 . Prvious studies have noted that progressive exercise has produced superior results when compared to minimal interventions (i.e., waitand-see) in terms of function in tendinopathies involving other tendons 44,45 .This finding reinforces the results found in our low heterogeneity analysis, suggesting that the natural history of the disease is not favorable for improving symptoms in individuals with tendinopathies and exercise-based interventions are important for clinical improvements.
Although some studies 40,41 have demonstrated similar benefits comparing resistance exercise to sham exercises (exercises which do not generate tension in the gluteus medius and minimus muscles), our analyses indicate that resistance exercise yields superior results in function/severity of symptoms.However, these results did not extend to quality of life.Studies included in the quantitative and qualitative analyzes that included education on load management and avoiding tendon compression as a co-intervention 37,38,40,41 showed favorable results in terms of clinical improvement.It is believed that activities or positions that cause prolonged or repetitive compression on tendons may worsen symptoms in patients with tendinopathy 28,46 .Therefore, it is possible that this education approach is an important aspect for the management of patients with gluteal tendinopathy.However, studies are needed to elucidate the isolated effects of education and exercise.
Furthermore, we found that the effect of exercise was similar to that of corticosteroid injections for short-and long-term pain intensity when the results of two clinical trials 38,39 were pooled in the meta-analysis.However, this analysis presented substantial heterogeneity and low certainty of evidence.Therefore, it is unclear which of these two treatment strategies is superior in terms of short-and long-term pain reduction.One high quality study, however, showed that exercise results in a higher treatment success rate when compared to corticosteroid infiltration both in the short-and long-term in individuals with gluteal tendinopathy 38 .This result corroborates with the existing evidence that resistance exercise is more effective than passive interventions in reducing pain and improving function in tendinopathies 17,45 .
Although the use of adjunct treatments such as corticosteroid injections is common in the treatment of gluteal tendinopathy, the real benefit of this approach is not yet well understood.A review that analyzed the effect of corticosteroid injections compared to no treatment concluded that corticosteroid injections have no significant effect on reducing pain and improving function in the short-and long-term 42 .Other studies indicate that the effects of corticosteroid injections are favorable in the short-term, however its benefits seem to decrease after 3 and 6 months 38,47 .
Various exercise modalities were investigated in the studies included in our analyses, such as isometric and kinetic chain exercises, isolated isometric and isotonic exercises, strengthening exercises with progressive load, functional exercises, stretching, and home exercises.Therefore, we cannot determine whether there is a specific type of exercise that is more favorable for the treatment of gluteal tendinopathy, since regardless of the modality, they all had positive effects in the outcomes studied.A pattern that we can see comparing all the included protocols is the fact that they all followed a daily exercise regimen and were carried out for 12 weeks [37][38][39][40][41] .What is not clear in all studies is how the initial exercise intensity was established and how this load was monitored and progressed.Normally in clinical trials involving exercises in the management of tendinopathies, the load is recommended to be gradually increased as long as there is no significant increase in pain (3-5/10 on a numerical pain scale) 17,48 .This approach seems to be an important aspect for the evolution of exercise intensity in tendinopathy 48 .
A recent review indicates that resistance exercises for the treatment of tendinopathies should involve progressive loads, reaching high intensities to ensure a sufficient mechanical stimulus to the tendon 48 .It was also pointed out that the time for recovery from the stimuli needs to be adequate 48 , which converges with the training frequency observed in current published protocols.Recent clinical trials have concluded that different exercise modalities result in reduced symptom severity and disability in tendinopathy 49,50 .However, because exercise is a complex treatment modality to apply, as it involves several parameters that need to be adjusted, more highquality clinical trials are necessary to define the ideal exercise dose for the treatment of gluteal tendinopathy.
The secondary outcomes qualitative analyses indicates that exercise-based interventions have positive effects in terms of hip abductor strength and pain catastrophizing in comparison to wait-and-see, based on the results of one high quality study 38 .These results are not surprising since increases in strength are expected after resistance exercises and it is plausible that with the process of gradual and progressive exposure to exercise, individuals decrease their excessive fear and catastrophizing thoughts.
This systematic review has strengths, such as the fact that it was conducted following the recommendations of the Cochrane Handbook for Systematic Reviews 26 , using the PRISMA checklist and flowchart 24 , and the GRADE approach to verify the certainty of evidence and strength of recommendations 36 .Furthermore, to our knowledge, no review has directly compared the effect of exercise to other conservative interventions for the treatment of gluteal tendinopathy.Therefore, the results of this study will help clinicians who work in the management of this condition to make assertive decisions based on evidence of high methodological rigor.
However, this review presents some limitations, especially in the development of meta-analyses.Because the outcomes of the different studies were not reported using the same measure (perception of treatment success, quality of life, level of physical activity, pain catastrophizing), it was not possible to make comparisons with these outcomes.Due to the small number of studies included, it was also impossible to group data to perform sensitivity and subgroup analyzes with the aim of exploring the potential effect of types of exercises, therapy dosage and population characteristics.Furthermore, publication bias was not assessed using funnel plots due to the limited number of studies included.Although studies indicate positive effects of exercise, the results of this review should be interpreted with caution because the certainty of the evidence ranged from low to very low.

Conclusion
Exercise-based interventions, including progressive loading and education are superior to minimal interventions (sham exercise or wait-and-see) in terms of short-and long-term function/symptom severity in individuals with gluteal tendinopathy.Regarding pain intensity, exercise-based interventions and corticosteroid infiltrations had similar effects in this population, however, exercise showed a higher treatment success rate when compared to corticosteroid infiltration both in the short-and long-term in individuals with gluteal tendinopathy.The certainty of the evidence varied from low to very low, therefore, large high-quality, randomized controlled trials are recommended.

Figure 1 .
Figure 1.Flowchart of review studies following PRISMA recommendations.RCT randomized clinical trial, PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Figure 2 .
Figure 2. Comparison between exercise and minimal intervention for short-and long-term function (A) and for quality of life in the short-and long-term (B).Comparison between exercise and corticosteroid injections (CI) for short-and long-term pain intensity (C).

Table 1 .
Samples, intervention characteristics, outcome measures, and adverse effects of the included studies.F female, ESWT extracorporeal shock wave therapy, CI corticosteroid injection, NRS numerical rating scale, GROC global rating of change, EQ-5D Euro Quality of Life Instrument-5D, HOOS Hip Disability and Osteoarthritis Outcome Score, OHS Oxford Hip Score, IPAQ-SF International Physical Activity Questionnaire Short Form; PCS Pain Catastrophizing Scale, BIP Brief Pain Inventory, VISA-G Victorian Institute of Sports Assessment-Gluteal, ADL Activity of Daily Living, QoL Quality of Life; PHQ9 Patient Health Questionnaire 9, LHPQ Lateral Hip Pain Questionnaire, PSFS Patient-Specific Functional Scale, AQol Assessment of Quality of Life instrument; AAS Active Australia Survey, MHT transdermal hormone replacement.

Table 2 .
Description of the studies considering the methodological characteristics, inclusion, and exclusion criteria of the included studies.RCT randomized clinical trial, IR internal rotation, BMI body mass index, CI corticosteroid injection, ER external rotation, FSH follicle-stimulating hormone, GTPS greater trochanteric pain syndrome, PRP platelet rich plasma, ESWT extracorporeal shock wave therapy, NSAIDs non-steroidal anti-inflammatory drugs, ROM range of motion, MRI magnetic resonance imaging, MHT transdermal hormone replacement.

Table 3 .
Analysis of risk of bias using the physiotherapy evidence based database (PEDro) scale from 0 to 10. Y yes, N no.

Table 4 .
Analysis of the certainty of evidence using grading of recommendations assessment (GRADE) on the effects of exercise on pain intensity, function, and quality of life in gluteal tendinopathy.All outcomes were downgraded due to Inaccuracy (less than 400 participants included in the analysis).-, did not evaluate the outcome.a Downgraded to indirect evidence: sample composed of postmenopausal women (> 52 weeks of menstrual cessation).Therefore, we cannot assume external validity for any individual with gluteal tendinopathy.b Downgraded to inconsistency: statistics I 2 was greater than 50%.